947 research outputs found
Listening for the Axion Echo with the 21 CentiMeter Array
The axion is a hypothetical elementary particle that could solve the
long-standing strong CP problem in particle physics and the dark matter mystery
in the cosmos. Due to the stimulation of the ambient photons, the axion dark
matter decay into photons is significantly enhanced so that its echo signal
could be detected by terrestrial telescopes. As a pathfinder, we study the
expected sensitivity of searching for the axion dark matter in the mass range
between and with the 21 CentiMeter Array (21CMA). We
aim to cover the whole 21CMA frequency range in two years by using a 1MW
emitter. We find that the resulting sensitivity on the axion-photon coupling
could surpass other existing limits by about one order of magnitude.Comment: 7 pages, 4 figure
Pax6 interactions with chromatin and identification of its novel direct target genes in lens and forebrain.
Pax6 encodes a specific DNA-binding transcription factor that regulates the development of multiple organs, including the eye, brain and pancreas. Previous studies have shown that Pax6 regulates the entire process of ocular lens development. In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific populations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification in telencephalon. In the pancreas, Pax6 is essential for the differentiation of α-, ÎČ- and ÎŽ-islet cells. To elucidate molecular roles of Pax6, chromatin immunoprecipitation experiments combined with high-density oligonucleotide array hybridizations (ChIP-chip) were performed using three distinct sources of chromatin (lens, forebrain and ÎČ-cells). ChIP-chip studies, performed as biological triplicates, identified a total of 5,260 promoters occupied by Pax6. 1,001 (133) of these promoter regions were shared between at least two (three) distinct chromatin sources, respectively. In lens chromatin, 2,335 promoters were bound by Pax6. RNA expression profiling from Pax6âș/â» lenses combined with in vivo Pax6-binding data yielded 76 putative Pax6-direct targets, including the Gaa, Isl1, Kif1b, Mtmr2, Pcsk1n, and Snca genes. RNA and ChIP data were validated for all these genes. In lens cells, reporter assays established Kib1b and Snca as Pax6 activated and repressed genes, respectively. In situ hybridization revealed reduced expression of these genes in E14 cerebral cortex. Moreover, we examined differentially expressed transcripts between E9.5 wild type and Pax6â»/â» lens placodes that suggested Efnb2, Fat4, Has2, Nav1, and Trpm3 as novel Pax6-direct targets. Collectively, the present studies, through the identification of Pax6-direct target genes, provide novel insights into the molecular mechanisms of Pax6 gene control during mouse embryonic development. In addition, the present data demonstrate that Pax6 interacts preferentially with promoter regions in a tissue-specific fashion. Nevertheless, nearly 20% of the regions identified are accessible to Pax6 in multiple tissues
Impact of Caloric Intake on Parenteral NutritionâAssociated Intestinal Morphology and Mucosal Barrier Function
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142275/1/jpen0474.pd
Low Molecular Weight Components in Aqueous Echinacea Purpurea Leaf Extract Inhibit Melanoma Cell Growth
Melanoma is a skin cancer associated with high mortality. The three year survival rate from advanced melanoma is between 10-15%. One reason for this high mortality rate is that melanoma cells are resistant to traditional chemotherapeutics. Echinacea is a plant genus native to North America with putative anticancer properties. Here, we examined effects of aqueous Echinacea purpurea leaf extract on the growth of melanoma cells and nontransformed fibroblasts. This aqueous extract reduced B16 mouse melanoma cell growth at concentrations that did not inhibit the growth of nontransformed NIH3T3 fibroblasts, suggesting that the extract had biological specificity against transformed cells. We also examined the effect of different fractions of the extract on melanoma cell growth. These data indicate that components less than 3 kD in size exhibited the greatest inhibitory action on melanoma cell growth. In addition, these data indicated that larger components in the extract ameliorate the ability of these low molecular weight compounds to inhibit melanoma cell growth. Furthermore, Echinacea extract inhibited the growth of v-Src transformed LA25 cells without reducing Src kinase activity. Taken together, these results suggest that aqueous Echinacea purpurea extract contains low molecular weight compounds that preferentially inhibit tumor cell growth in the face of oncogenic tyrosine kinase activity. These data suggest future studies to better define bioactive compounds in Echinacea purpurea and evaluate their therapeutic efficacy in vivo
We lose ground: Global assessment of land subsidence impact extent
Depletion of groundwater aquifers along with all of the associated quality and quantity problems which affect profitability of direct agricultural and urban users and linked groundwater-ecosystems have been recognized globally. During recent years, attention has been devoted to land subsidenceâthe loss of land elevation that occurs in areas with certain geological characteristics associated with aquifer exploitation. Despite the large socioeconomic impacts of land subsidence most of these effects are still not well analyzed and not properly recognized and quantified globally. In this paper we developed a land subsidence impact extent (LSIE) index that is based on 10 land subsidence attributes, and applied it to 113 sites located around the world with reported land subsidence effects. We used statistical means to map physical, human, and policy variables to the regions affected by land subsidence and quantified their impact on the index. Our main findings suggest that LSIE increases between 0.1 and 6.5% by changes in natural processes, regulatory policy interventions, and groundwater usage, while holding all other variables unchanged. Effectiveness of regulatory policy interventions vary depending on the lithology of the aquifer system, in particular its stiffness. Our findings suggest also that developing countries are more prone to land subsidence due to lower performance of their existing water governance and institutions.Partial funding was provided by the Giannini Foundation of Agricultural Economics Minigrant Program. Dinar would like to acknowledge support from the W4190 Multistate NIFA-USDA-funded Project, âManagement and Policy Challenges in a Water-Scarce World.â Esteban, Calvo, and Albiac would like to acknowledge support from the project INIA RTA2017-00082-00-00 by the Spanish Ministry of Science and Innovation, and support by funding to the research group ECONATURA from the Government of Aragon. TomĂĄs would like to acknowledge support from the Spanish Ministry of Economy and Competitiveness, the State Agency of Research and the European Funds for Regional Development under project TEC2017-85244-C2-1-P. TomĂĄs, Herrera, Ezquerro, and Teatini acknowledge the European Union support from the RESERVOIR project (GA nÂș 1924) developed in the framework of the PRIMA program
EficĂĄcia de Metformina em doentes com diabetes tipo II, relacionado com variantes do gene SLC22A1
La diabetes mellitus tipo II (DM II) es una enfermedad que afecta una gran cantidad de individuos. Un medicamento empleado en el tratamiento de los pacientes es la metformina. Este medicamento es transportado al interior de los hepatocitos por un transportador codificado por el gen SLC22A1. Variantes en el gen con actividad reducida pueden disminuir la cantidad de metformina disponible en el hĂgado y reducir la respuesta terapĂ©utica. Se propuso evaluar diferentes parĂĄmetros bioquĂmicos en relaciĂłn a la dosis de metformina y la presencia de variantes en el transportador. Se estudiaron 103 pacientes mayores de 18 años con diagnĂłstico de DM II, tratados con 1700 mg/ dĂa de metformina por mĂĄs de 6 meses. Se analizaron 5 polimorfismos en el gen SLC22A1, glucemia, HbA1c, funciĂłn hepĂĄtica, perfil lipĂdico y renal. Los niveles de HbA1c y de glucemia fueron mĂĄs elevados en los pacientes que presentaban los polimorfismos R61C, G401S, M420del y G465R aunque la diferencia fue estadĂsticamente significativa sĂłlo para la HbA1c en los pacientes que presentaban las variantes M420del y G465R (p=0,0273 y 0,0018, respectivamente). La presencia de polimorfismos con actividad reducida en el gen SLC22A1 afecta los niveles de glucemia y de HbA1c en pacientes con DM II cuando son tratados con metformina.Diabetes mellitus type II (DM II) is a disease that affects a large number of individuals. One of the drugs used for the treatment is metformin. Metformin is delivered into hepatocytes by a transporter encoded by the SLC22A1 gene. Gene variants with reduced activity may decrease the amount of metformin available in the liver and reduce the therapeutic response. Various biochemical parameters were evaluated in relation to the metformin dose and the presence of transporter variants. A total of 103 patients older than 18 diagnosed with DM II who were treated with 1700 mg/day of metformin for more than six months were studied. Five polymorphisms in the SLC22A1 gene were analyzed as well as glycemia, HbA1c level, liver function, and lipid and kidney profiles. HbA1c and glycemia levels were higher in patients with the R61C, G401S, M420del and G465R polymorphisms; although the difference was statistically significant only for HbA1c in patients with the M420del and G465R variants (p=0.0273 and 0.0018, respectively). Polymorphisms with reduced activity in the SLC22A1 gene affect blood glucose levels and HbA1c in patients with DM II when they are treated with metformin.O diabetes mellitus tipo II (DM II) Ă© uma doença que afeta uma grande quantidade de indivĂduos. Um medicamento utilizado no tratamento dos doentes Ă© a metformina. Esse medicamento Ă© transportado no interior dos hepatĂłcitos por um transportador codificado pelo gene SLC22A1. Variantes no gene com atividade reduzida podem diminuir a quantidade de Metformina disponĂvel no fĂgado e reduzir a resposta terapĂȘutica. PropĂŽs-se avaliar diferentes parĂąmetros bioquĂmicos em relação Ă dose da metformina e Ă presença de variantes no transportador. Foram estudados 103 pacientes maiores de 18 anos com diagnĂłstico de DM II tratados com 1700 mg/dia de metformina por mais de 6 meses. Foram analisados 5 polimorfismos no gene SLC22A1; glicemia, HbA1c, função hepĂĄtica, perfil lipĂdico e renal. Os nĂveis de HbA1c e de glicemia foram superiores em doentes que apresentavam os polimorfismos R61C, G401S, M420del e G465R; embora a diferença seja estatisticamente significativa apenas para o HbA1c nos doentes que apresentavam as variantes M420del e G465R (p=0,0273 e 0,0018; respectivamente). A presença de polimorfismos com atividade reduzida no gene SLC22A1 afeta os nĂveis da glicemia e do HbA1c em doentes com DM II quando sĂŁo tratados com metformina.Fil: Yang, Pablo. Universidad Catolica de CĂłrdoba. Facultad de Ciencias QuĂmicas; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: NicolĂĄs, Juan Carlos. Universidad Catolica de CĂłrdoba. Facultad de Ciencias QuĂmicas; ArgentinaFil: GalvĂĄn, Cristian Ariel. Universidad Catolica de CĂłrdoba. Facultad de Ciencias QuĂmicas; ArgentinaFil: VĂ©lez, Pablo. Provincia de CĂłrdoba. Ministerio de Ciencia y TĂ©cnica. Centro de Excelencia En Productos y Procesos de CĂłrdoba; ArgentinaFil: Da Ronco, Luciano. Laboratorio de AnĂĄlisis ClĂnicos Especializados
; ArgentinaFil: DĂaz, Gustavo Tomas. Centro MĂ©dico San Ricardo Pampurri; ArgentinaFil: Beltramo, Dante Miguel. Universidad Catolica de CĂłrdoba. Facultad de Ciencias QuĂmicas; Argentina. Provincia de CĂłrdoba. Ministerio de Ciencia y TĂ©cnica. Centro de Excelencia En Productos y Procesos de CĂłrdoba; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Soria, NĂ©stor Walter. Universidad Catolica de CĂłrdoba. Facultad de Ciencias QuĂmicas; Argentin
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